고려대학교 구로병원 김현구 two vs. three field lymph node dissection in surgery for...

고려대학교 구로병원 김현구

Two vs. Three Field Lymph Node Dissection in Surgery for

Esophageal Cancer

Incision vs. LN Dissection

Ivor-Lewis Two-holeTwo-inci-sion

Two-field

McKweon Three-hole Tri-inci-sion

Three-field

Case-1

M/61G-fiber: 39cm from incisorBiopsy: Squamous cell carci-nomaStage: cT1N0M0

Treatment?

Case-2

M/63G-fiber: 25~28cm from incisorBiopsy: severe dysplasia with leiomyomaStage: cT1N0M0

Treatment?

Case-3

M/49G-fiber: 26~28cm from incisorBiopsy: Squamous cell carci-nomaStage: cT1N0M0

Treatment?

Two-Field or Three-Field ?

Tumor locationDepth of tumor inva-sionTumor cell type

Substantial morbidityPrognostic benefitQuality of life

Tumor locationDepth of tumor inva-sionTumor cell type

Optimal Surgical Extent ?

• Systemic dis-ease

• Palliative• Advancement

of

chemotherapy &

radiotherapy

Minimal

• Advancement of

operative tech-nique• Advancement

of

perioperative

management

Radical

Categorization of Esophageal Seg-ment

Cervical

Upper thoracic

Mid thoracic

Lower thoracic

Abdominal

Lymphatic Drainage

Multidirectional lymphatic flow

Lymphatic Drainage

Regional lymphatics (N1)

Submocosal plexusRegional (N1) & non-regional lymph nodes (M1a & M1b)

Thoracic duct & thesystemic venous circula-tion (M1b)

Abundant lymph-capillary network in the submucosal longitudinal lymphatic drainage (vs. segmental in colon ca.) Rice TW, Lancet, 1999, Hosch SB, JCO,

2001, Lerut, Ann Surg, 2004

Lymph-capillary network in submucosal space

☞Widespread and random patterns of lymph node metastasis Ando N, Ann Surg, 2000

Skip metastasis: 50~60% MatsubaraT, Cancer, 2000

Lymph Node Mapping System

Lymph Node Mapping System

N Regional Lymph Nodes

NX Regional lymph nodes cannot be assessed.

NO No regional lymph node metastases

N1 Regional lymph node metastases

M Distant Metastasis

MX Distant metastases cannot be assessed.

M1a: Upper thoracic esophagus metastatic to cervical lymph nodes

  Lower thoracic esophagus metastatic to celiac lymph nodes

M1b Upper thoracic esophagus metastatic to other nonregional lymph nodes or

other distant sites

  Midthoracic esophagus metastatic to either nonregional lymph nodes or

other distant sites

  Lower thoracic esophagus metastatic to other nonregional lymph nodes or

other distant sites

Patterns of Metastatic Nodal Spread

Association with tumor loca-tion-1

Akiyama H, Ann Surg 1994. Altorki N, Ann Surg 2002

Patterns of Metastatic Nodal Spread

☞ 3-field LN dissec-tion

Association with tumor location-2

Kato H, J Surg Oncol 1991

Sharma S, Surg Today 1994

Patterns of Metastatic Nodal Spread

☞ 2-field LN dissec-tion

Nodal metastasis is a rare find-ing three levels away from the location of the tumor. It is most common in the same level as the tumor and one level adja-cent to the tumor. The involve-ment of lymph nodes that are two levels away from the loca-tion of the tumor is also very common but to a lesser extent.

Patients with carcinoma in the upper thoracic esophagus rarely had metastasis in the abdominal nodes, while those with carci-noma in the lower thoracic esophagus rarely had metastasis in the cervical nodes.

Association with depth of tumor inva-sion-1

Rice TW, Ann Thorac Surg 1998

Patterns of Metastatic Nodal Spread

Association with depth of tumor inva-sion-2

Matsubara T, Br J Surg 1999

Patterns of Metastatic Nodal Spread

☞ T stage ↑→ LN Metasta-sis↑

Association with tumor cell type

Sheids 6th edi-tion

Patterns of Metastatic Nodal Spread

☞ No difference

Axial margin

Siu KF, Ann Surg 1986 Law S, Am J Surg 1998

Extent of Resection

Taking account shrinkage of the specimen after resection as a guide to surgery, an in-situ margin of 10cm (fresh contracted specimen of ~5cm) should be aimed to, allow a less than 5% chance of anas-tomotic recurrence.

Lymphadenectomy

Pearson, 3rd edi-tion

Extent of Resection

Standard2-field

Extended2-field

Total2-field

Mediastinal lymph node dissection

Abdominal lymph node dissection

Cervical lymph node dissection

or

Cervical Esophagus

Distant metastasis: 20%Regional metastasis: 63%Median survival: 11~14months5-year survival: 14~21%5-year survival was significantly low when re-gional neck LN involved (8% vs. 38%)

However, regional LN involvement was not prognostic parameter in multivariate analysis

Marmuse JP, Am J Surg, 1995Triboulet JP, Arch Surg, 2001

Upper Thoracic Esophagus

In resectable T3 squamous cell carcinoma,

Manshanden CG Eur J Surg Oncol 2000Igaki H, Br J Surg 2005

☞ Although cervical lymph node dissection is important for staging, curative surgery for cervical-upper esophageal cancer combined with extended lymph node dissection is probably only indicated in selected cases without distant lymph node metastasis.

Bresadola F, ORL J Otorhinolaryngol Relat Spec 2001

o

No differ-ence

Limited resec-tion

Ex-tended LN dis-section

3-year survival

14%

20%

Middle & Lower Thoracic Esophagus

In Japan, 70% of the esophageal carcinoma occurs in the middle tho-racic esophagus.

Ando N, Ann Surg 2000

Tachibana M, Am J Surg 2005Nine of 141 patients with middle esophageal cancer had cervico-tho-racic nodal involvement.→3-field LN dissection proved to be important for correct staging.

In lower thoracic esophageal carcinoma, no patient had cervico-up-per thoracic LN involvement.→ Patients with negative upper thoracic LN not necessarily have to undergo a 3-field LN dissection.

Involved celiac nodes were found in tumors at all three locations.→ For esophageal tumors investigation of celiac LN is worthwhile.

Cervical LN Metastasis in Esophageal Cancer

1. 14~30% patients: metastasis to cervical lymph nodes40% for upper third tumors20% for lower third tumors

2. Frequency of nodal metastasis: increased with depth of tumor penetration

Intramucosa < submucosa < muscularis propria < adventitia 30% < 50% < 60% < 80%

3. LNs in both recurrent laryngeal nerves frequently have metastasis.

Isono K, 1991, Oncology

☞ Extended radical esophagectomy with 3-field LN dissection☞ Improving accuracy of staging & better local control

5 –Year Survival in 2- vs. 3-Field LN Dissection

Akiyama H, Am J Surg. 1984

2-Field 3-Field p

- Node 55% 84% 0.004

+ Node 28% 43% 0.008

Skeptical Views to 3-Field LN Dis-section-1

1. Systemic disease Replaced by neoadjuvant chemotherapy or intraoperative radiother-

apy

2. Hospital mortality: 4% Increased morbidity: 44.8% Recurrent laryngeal nerve palsy: 16~58% Pulmonary complication: 21.3% Anastomotic leak: 19~30% Septic complication: 27%

Decreased QOL Severe hoarseness, restricted food intake, reduced exercise tolerance:

20%

Skeptical Views to 3-Field LN Dis-section-2

3. No prognostic benefit Recurrence rate in cervical LN: 11% Isolated cervical nodal recurrence: 4% vs. Mediastinum(21%), systemic organ metastasis(26%) ☞ Minimal role of cervical LN dissection

4. Prospective Randomized study

2-Field 3-Field p

Nishihira T, Am J Surg, 1998

48% 65% NS

National cancer hos-pital in Tokyo

33% 48% 0.3

LN Dissection along Recurrent Laryn-geal Nerve

Recurrent laryngeal LN + cervical LN → Cervicothoracic group

Selective 3-Field LN Dissec-tion

Sentinel Lymph Node

The first lymph node within the lymphatic basin reached by lymph draining from the primary lesion

Limited Reports

Complicated compared to gastric cancer

Limited No. of early esophageal can-cer

The frequency of metastasis in SLN was significantly higherLN involvement was found in only 2% of the non-SLN

Kitagawa Y, Surg Clin North Am 2000

The preoperative mapping of SLN based on the lym-phoscintigraphy Improved the accuracy of the intraoperative gamma probing

Baciewicz FA, Jr., J Invest Surg 2000

Procedure Preoperation

1 day before surgeryRadioisotope injec-

tion

4 hours after injec-tion

Lymphoscintigram

Kitagawa, Gen Thorac Cardiovasc Surg, 2008

Procedure Intraoperation

Percutaneous gamma prob-ing

Gamma probing through thoracotomy or thora-

coscopy

Dual tracer methodRadioisotope Blue dye: endoscopically in-

jection right before surgery

SLN Mapping in Esophageal Cancer

1. Predict overall lymph node status

2. Tailored extent of lymphadenectomy Avoid unnecessery morbidity and mortality for node- negative patientsMore radical treatment for node-positive patients

3. More detailed examination to optimize disease staging of target specific nodal tissue

Step sectioningImmunochemistryRT-PCR

4. Determination of the radiation field during CCTR

SLN Mapping in EMR

Organ preservation treatment: EMR, PDT, Argon plasma coagulation

KUGH Experiences

Sex

Age Location CCRT C-StageP-

StageOperation SLN

No. of SLN

Metastasis

M 65 Lower NoT1N0M

0T3N1M

0Ivor-Lewis 8, 17, 20 3 17

F 56 Lower NoT1N0M

0T3N0M

0Ivor-Lewis 9 1 no

M 64 Lower NoT1N0M

0T1N0M

0Ivor-Lewis 7, 8, 10, 17 4 no

M 64 Middle YesT1N0M

0T0N0M

0McKeown 3p 1 no

M 65 Lower NoT1N0M

0T3N0M

0Left

thoracotomy17, 18 2 no

M 61 Lower NoT1N0M

0T2N0M

0Ivor-Lewis 20 1 no

M 48 Middle YesT3N0M

0T0N0M

0Ivor-Lewis 4 1 no

M 60 Upper YesT2N0M

0T2N0M

0McKeown 1, 8, 9 3 no

M 70 Middle NoT2N0M

0T3N1M

0McGweon 1, 2, 4, 7, 8 5 2

M 65 Middle NoT1N0M

0T2N0M

0McGweon 1, 7 2 no

M 46 Middle NoT2N0M

0T2N0M

0McGweon 7, 8 2 no

M 50 Lower NoT2N0M

0T2N1M

0Ivor-Lewis

7, 8, 9, 16, 18

5 16

M 58 Lower NoT2N0M

0T3N1M

0Ivor-Lewis 7 1 16

Duration: November 2007 ~ March 2009Patients: T1~3 N0M0 squamous esophageal cancerRadioisotope: 99mTc-neomannosyl human serum albumin (99mTc-MSA)

Results

No. of sentinel lymph node 2.4±1.50 (1~5)

Detection rate 100%

False-negative SLN 1/ 13 (7.7%)

Conclusions

Curative surgery for cervical-upper esophageal cancer com-bined with extended LN dissection is probably only indicated in selected cases without distant LN metastasis.

3-field LN dissection proved to be important for correct stag-ing in middle esophageal cancer.

In lower thoracic esophageal carcinoma, patients with nega-tive upper thoracic LN not necessarily have to undergo a 3-field LN dissection.

No statistical difference in survival was found in randomized trials comparing an extensive LN dissection with a limited lymphadenectomy.

Selective LN dissection using sentinel lymph node mapping have to be further evaluated before it can be applied widely.

THANK YOU !